SAN FRANCISCO -- An investigational hepatitis C drug was safe and effective in a small randomized trial, a researcher said here.

Action Points

Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Explain that an investigational hepatitis C virus (HCV) drug (TMC435), a second-generation protease inhibitor given once a day, was safe and effective in a phase IIB randomized trial.

Note that there was no major difference in adverse events between the treatment and placebo arms of the trial.

SAN FRANCISCO -- An investigational hepatitis C virus (HCV) drug -- a second-generation protease inhibitor given once a day -- was safe and effective in a phase IIB randomized trial, a researcher said here.

Between 75% and 86% of patients treated with TMC435 had undetectable hepatitis C RNA after 24 weeks of treatment, depending on dose, reported Michael Fried, MD, of the University of North Carolina in Chapel Hill.

In addition, there was no major difference in adverse events between the treatment and placebo arms in the PILLAR (Protease Inhibitor TMC435 trial assessing the optimaL dose and duration as once daiLy Anti-viral Regimen) trial, Fried said at a late-breaker session during the annual meeting of the American Association for the Study of Liver Diseases.

The primary endpoint of the study was the proportion of patients with undetectable hepatitis C RNA at week 72, which was 24 weeks after the end of treatment, Fried said. However, his presentation here focused on what he said was "the most clinically meaningful endpoint," which was the rate of undetectable hepatitis C RNA at week 24.

The researchers enrolled 386 patients with the difficult-to-treat genotype 1 of hepatitis C and randomly assigned them to placebo or one of two doses of TMC435: 75 or 150 mg daily.

All patients were also given standard therapy with pegylated interferon-alfa and ribavirin for at least the first 24 weeks of the study. Depending on response, some patients in the treatment arms stopped the treatment or were given an additional 24 weeks. Patients in the control arm had 48 weeks of interferon and ribavirin.

Within each TMC435 dosing group, patients were randomly assigned to get 12 or 24 weeks of the drug.

In an intention-to-treat analysis, the researchers found:

82% of patients in the 12-week, 75-mg arm had undetectable hepatitis C RNA after 24 weeks.

In the 150-mg dosing group, 81% in the 12-week arm and 86% in the 24-week arm reached the same endpoint.

The differences from placebo were significant at P<0.005, P=0.013, and P<0.001, respectively.

Interestingly, the 75% response in the 24-week, 75-mg arm was not significantly different from the "unexpectedly high" 65% response rate among the placebo patients, Fried said.

A key finding was that between 79% and 86% of the patients receiving the drug qualified for shortened 24-week therapy, "which I think is quite beneficial," Fried said. Of those, he said, between 85% and 96% had undetectable hepatitis C RNA at week 24.

All patients had at least one adverse event, Fried said, with 3.6% of such events leading to study discontinuation in the TMC435 arms, compared with 5.2% in the control arm. The rate of grades 3 and 4 events was similar between the treatment and placebo arms. However, 6.5% of adverse events were judged as serious in the TMC435 group compared with 13% among placebo patients.

Most adverse events, including rash, anemia, and neutropenia, were similar between the arms.

The compound is the "front-runner" in the second generation of protease inhibitors and clinicians are watching its progress closely, according to Norah Terrault, MD, of the University of California San Francisco, who was not part of the study but was one of the moderators of the session at which it was presented.

"This is the next step for us if we are going to use peginterferon and ribavirin," she told MedPage Today. "It is clearly going to offer an advantage over current therapies."

One advantage, she said, is that once-daily dosing -- compared with three times a day for the currently approved drugs -- should improve patient adherence to their treatment regimen.

As well, she added, the "side effect profile looks very good" with no additional burden of rash or anemia.

On the other hand, a range of new drugs is in development and some can be given without interferon. Clinicians may soon be able to choose interferon-free strategies to treat hepatitis C, Terrault said.

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